RESUMO
Persistence of rubella live vaccine has been associated with chronic skin granuloma in 3 children with primary immunodeficiency. We describe 6 additional children with these findings, including 1 with visceral extension to the spleen.
Assuntos
Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/etiologia , Síndromes de Imunodeficiência/complicações , Vacina contra Rubéola/efeitos adversos , Biópsia , Proteínas do Capsídeo/genética , Criança , Feminino , Proteínas de Homeodomínio/genética , Humanos , Imuno-Histoquímica , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Masculino , Mutação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vacina contra Rubéola/genética , Pele/patologia , Pele/virologia , Baço/patologia , Baço/virologiaRESUMO
BACKGROUND: Evaluation of long-term tolerance to antiretroviral exposure during pregnancy is required. An increased risk of cancer has been suggested in children exposed in utero to didanosine. METHODS: Updated evaluation of cancer incidence in uninfected children exposed to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) in the French perinatal study of children born to HIV+ mothers, by cross-checking with the National Cancer Registry. Associations between cancer risk and exposure to NRTIs were evaluated by univariate survival analysis and Cox proportional hazard models. Standardized incidence ratios (SIR) were used for comparison with the general population. RESULTS: A total of 21 cancers were identified in 15â163 children (median age: 9.9 years [interquartile range (IQR): 5.8-14.2]) exposed to at least one NRTI in utero, between 1990 and 2014. Five children were exposed to zidovudine monotherapy, and 16 to various combinations, seven including didanosine. Didanosine accounted for only 10% of prescriptions but was associated with one-third of cancers. In a multivariate analysis, didanosine exposure was significantly associated with higher risk [hazard ratioâ=â3.0 (0.9-9.8)]. The risk was specifically linked with first-trimester exposure [hazard ratioâ=â5.5 (2.1-14.4)]. Overall, the total number of cases was not significantly different from that expected for the general population [SIRâ=â0.8 (0.47-1.24)], but was twice that expected after didanosine exposure [SIRâ=â2.5 (1.01-5.19)]. CONCLUSION: There are strong arguments to suggest that didanosine displays transplacental oncogenicity. Although not extrapolable to other NRTIs, they stress the need for comprehensive evaluation of the transplacental genotoxicity of this antiretroviral class.
